Project Summary This proposal requests funds for the upgrade of an existing 600 MHz NMR spectrometer with a modern console and a helium-cooled cryogenic quadnuclear (1H, 13C, 15N, 31P) probe. The proposed upgrade will utilize the existing ultra-shielded magnet while replacing the spectrometer console and probes that are 18 years old, malfunctioning, and no longer supported by the manufacturer. While this instrument was once highly utilized, the failure of the original cryoprobe, and the outdated hardware and software of this instrument, have severely limited its functionality. The proposed upgrade will recapture critical capabilities that were lost to many research groups when the old cryoprobe failed irreparably. The upgrade will also add new capabilities that were not available. This includes analysis of the many limited quantity samples of complex molecules that are common to many different research groups. The enhanced sensitivity of the instrumentation will greatly improve productivity across a large user group. This new spectrometer will upgrade the existing 1H-detection triple-resonance (HCN) capability, in terms of detection sensitivity by 650%, for structural characterization of biomolecular protein and peptides. New capabilities of the proposed instrument include optimized 13C and 31P detection with proton decoupling for low concentration and unstable samples. Correlation between 13C and 31P, which is critical to organometallic and structural biology applications, will be enabled by the proposed spectrometer. Besides new capabilities introduced, a proposed auto-sampler coupled with a new biomolecular NMR automation package will allow a broad group of users to acquire high quality NMR data using this instrument. The proposed instrument will provide benefit to a large user base of NIH supported researchers that spans the areas of organic chemistry, organometallic chemistry, biochemistry, biomaterials, chemical biology, and glycoscience. Projects to be facilitated by this grant will have impact on the nation's health interests in drug discovery, radiochemical imaging, cancer therapy, tissue regeneration and drug delivery. Descriptions of research projects by ten major users and five minor users of the proposed instrumentation are described. The majority of users are investigators on currently funded NIH supported research projects. This instrumentation will also provide substantive support to several major NIH initiatives centered at the University of Delaware, including a Chemistry Biology Interface (NIH-CBI) Program, two Centers of Biomedical Research Excellence (NIH-COBRE), the Delaware IDeA Network of Biomedical Research Excellence (NIH-INBRE), and a Center for Translational Research (NIH-CTR). !